Embryonic stem cells (ES cells) are stem cells established from human or mouse early embryos which have a characteristic feature that they can be cultured over a long period of time while maintaining pluripotent ability to differentiate into all kinds of cells existing in living bodies. Human embryonic stem cells are expected for use as resources for cell transplantation therapies for various diseases such as Parkinson's disease, juvenile diabetes, and leukemia, taking advantage of the aforementioned properties. However, transplantation of ES cells has a problem of causing rejection in the same manner as organ transplantation. Moreover, from an ethical viewpoint, there are many dissenting opinions against the use of ES cells which are established by destroying human embryos. If dedifferentiation of patients' own differentiated somatic cells could be induced to establish cells having pluripotency and growth ability similar to those of ES cells (in this specification, these cells are referred to as “induced pluripotent stem cells (iPS cells)”, though they are sometimes called “embryonic stem cell-like cells” or “ES-like cells”), it is anticipated that such cells could be used as ideal pluripotent cells, free from rejection or ethical difficulties.
As a method for reprogramming a somatic nucleus, for example, a technique of establishing an embryonic stem cell from a cloned embryo, prepared by transplanting a nucleus of a somatic cell into an egg, was reported (W. S. Hwang et al., Science, 303, pp. 1669-74, 2004; W. S. Hwang et al., Science, 308, pp. 1777-83, 2005: these articles were, however, proved to be fabrications and later withdrawn). However, this technique of preparing the cloned embryo only for the purpose of establishing ES cells, has rather more serious ethical problems when compared with ordinary ES cells using surplus embryos produced in fertilization therapy. A technique of reprogramming a somatic cell nucleus by fusing a somatic cell and an ES cell was also reported (M. Tada et al., Curr. Biol., 11, pp. 1553-1558, 2001; C. A. Cowan et al., Science, 309, pp. 1369-73, 2005). However, this method results in the use of human ES cells, which fails to provide a solution to the ethical difficulties. Further, a technique of reprogramming a cell nucleus by reacting an extract of a cell strain, derived from a germ cell tumor generated in a human, with a differentiated cell was reported (C. K. Taranger et al., Mol. Biol. Cell, 16, pp. 5719-35, 2005). However, it was completely unknown which component in the extract induced the reprogramming in this method, and therefore, this method has problems of technical reliability and safety.
A method for screening a nuclear reprogramming factor having an action of reprogramming differentiated somatic cells to derive induced pluripotent stems cell was proposed (International Publication WO2005/80598). This method comprises the steps of contacting somatic cells containing a gene, in which a marker gene is positioned so as to receive expression control by an expression control region of the ECAT (ES cell associated transcript) genes (i.e., a class of genes specifically expressed in ES cells), with each test substance; examining presence or absence of the appearance of a cell that expresses the marker gene; and choosing a test substance inducing the appearance of said cell as a candidate of a nuclear reprogramming factor for somatic cells. A method for reprogramming a somatic cell is disclosed in Example 6 and the like of the above publication. However, this publication fails to report an actual identification of a nuclear reprogramming factor.
Patent document 1: International Publication WO2005/80598